The stability of bone implants and particularly endosseous tooth implants depends greatly on the ingrowth properties of the implant material. Implant articles and synthetic bone matrices are therefore often provided as highly porous structures of bone-mimetic materials with bioactive coatings. The osteointegration process of an implant into the surrounding bone is complex and involves adaptive cellular responses such as differentiation, migration, attachment, proliferation, extracellular matrix synthesis and finally mineralization of the matrix. Bone sialoprotein (BSP), a phosphorylated 70-80 kDa phosphorylated glycoprotein, is beside osteocalcin and osteonectin the major non-collagenous protein in the extracellular matrix of bone (Fisher L W, Termine J D 1985 Noncollagenous proteins influencing the local mechanisms of calcification, Clin Orthop 200:362-385; Marks S C, Popoff S N 1988 Bone cell biology: The regulation of development, structure, and function in the skeleton. Am J Anat 183:1-44). The expression of BSP coincides with initial bone mineralization (Hunter G K, Goldberg H A 1993 Nucleation of hydroxyapatite by bone sialoprotein. Proc Natl Acad Sci USA 90:8562-8565; Hunter G K et al. 1994 Modulation of crystal formation by bone phosphoproteins: Role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein. Biochem J 302:175-179; Hoshi K, Ozawa H 2000 Matrix vesicle calcification in bones of adult rats. Calcif Tissue Int 66:430-434). Moreover, it was shown that BSP is osteoinductive when coated onto femoral implants (OToole G C et al, 2004, Bone sialoprotein-coated femoral implants are osteoinductive but mechanically compromised. J Orth Res 22:641-646.).
U.S. Pat. No. 5,478,237 (Ishikawa) describes a titanium implant provided with a layer of bioactive hydroxyapatite, WO 02/078759 (Stratec Medical AG et al.) an implant with a porous metal oxide layer comprising amorphous and nanocrystalline calcium phosphate and hydroxyapatite, WO 02/085250 (KERAMED GmbH) an implant provided with a metabolically activating coating comprising resorbable calcium phosphate phases as well as adhesion and signal proteins such as bone sialoprotein (BSP), bone morphogenic proteins (BMP), fibronectin, osteopontin (OPN), ICAM-I VCAM und functional derivatives thereof. Other metallic implants of this kind are described in EP 1 166 804 A2 (Merck, Darmstadt) and WO 99/08730 (Children's Medical Center Corporation). DE 100 37 850 A1 (Jenissen H) and WO 03/059407 A1 (Straumann Holding A G) describe the application of ubiquitin, transforming growth factor (TGF) and other systemic hormones such as osteostatin, osteogenie and osteogrowth peptide (OGP) on implants. US 2004-0033249 teaches metal implants with a biomimetically produced bone-analogous coating comprising a collagen matrix mineralised with calcium phosphate, EP 1 442 755 A1 (Depuy Products) a bioactive ceramic surface coating into which biological agents are incorporated, amongst others, the osteogenic proteins OP-1, BMP-7 and non-collagenous bone matrix proteins. Further mentioned have been fibroblast growth factor (FGF), transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), insulin growth factor (IGF) and family members of the foregoing. The osteointegration activity of these bioactive molecules, however, is mere speculation because their osteointegrating activity cannot be measured, neither in vitro nor in vivo. Bone-mimetic surface layers on implant articles suffer from the disadvantage that they loosen from the substrate with time which affects in particular the long-term stability of the implant. On the other hand there is strong evidence that metal implants inhibit the necessary differentiation of the mesenchymal stem cells to osteoblasts especially when the implants have worked surfaces and thus bear small abrasion particles (Wang et al., J. Orthopedic. Res., 2002, 20, 1175-84).
In practice, aseptic loosening of endosseous implants remains an unsolved problem, long-term stability too and osteointegration properties of the implant in general. Despite the known bioactive coatings there is regularly a considerable time lag between surgery and commencement of the bone healing processes so that endosseous tooth implant must remain unloaded for months after placement before they withstand the typical pressure, shear and tensile forces.